bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2025–12–28
seven papers selected by
Muhammad Rizwan, COMSATS University
  1. Extracellular vesicles-derived non-coding RNA in leukemias and pre-leukemic syndromes: a systematic review.
  2. "Exosomal blueprint of lung-tropic metastasis: molecular signatures, microenvironmental conditioning, and translational implications in cancer".
  3. The role of exosomal long non-coding RNAs in head, neck and thyroid cancers.
  4. Exosomal non-coding RNAs as emerging drivers of immune dysregulation in melanoma.
  5. Therapeutic potential of microRNA let-7a-enriched exosomes in modulating macrophage plasticity (M1) and inhibiting malignant tendencies in breast cancer.
  6. Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.
  7. Recent Advances in Theranostic-based Extracellular Vesicles in Cancer Stem Cell Diagnosis and Therapy.
  1. J Cancer Res Clin Oncol. 2025 Dec 23. 152(1): 20
    Extracellular vesicles-derived non-coding RNA in leukemias and pre-leukemic syndromes: a systematic review.
    Narjes Seddighi, Malihe Najafpour, Mohammadreza Riyahi, Sepideh Mahmoudzadeh, Mehdi Talebi.
       BACKGROUND: Hematological malignancies, including leukemia, lymphoma, and multiple myeloma, are among the most aggressive cancers, with high mortality rates and limited early diagnostic tools. Exosomes, nano-sized extracellular vesicles secreted by numerous cells including tumor cells, have emerged as promising biomarkers due to their stability, non-invasive isolation, and disease-specific molecular cargo, particularly non-coding RNAs (ncRNAs).
    METHOD: This systematic review, conducted following PRISMA 2020 guidelines, evaluated the diagnostic and prognostic potential of exosomal ncRNAs in hematological malignancies by analyzing 16 studies from five databases (Scopus, PubMed, Embase, Web of Science, and ProQuest).
    RESULT: Key findings revealed that exosomal microRNAs, such as miR-532, miR-10b, and miR-21 in acute myeloid leukemia, miR-326 in acute lymphoblastic leukemia, and miR-494 in chronic myeloid leukemia, exhibit significant differential expression between patients and healthy controls, correlating with disease progression, treatment resistance, and survival outcomes. Moreover, long non-coding RNAs and circular RNAs were identified as potential biomarkers in myelodysplastic syndromes and leukemia. This review highlights the role of exosomal ncRNAs in liquid biopsies for early detection and monitoring. However, heterogeneity in isolation methods and sample sizes emphasizes the need for standardized protocols.
    CONCLUSION: These findings highlight the transformative potential of exosomal ncRNAs in precision oncology, offering novel ways for non-invasive diagnostics, prognostic stratification, and targeted therapies in hematological malignancies. Additional studies are necessary to validate these biomarkers and explore their clinical applications.
    Keywords:  Biomarkers; Exosomes; Hematological malignancies; Liquid biopsy; Non-coding RNAs; Precision medicine
    DOI:  https://doi.org/10.1007/s00432-025-06385-6
  2. Med Oncol. 2025 Dec 26. 43(2): 93
    "Exosomal blueprint of lung-tropic metastasis: molecular signatures, microenvironmental conditioning, and translational implications in cancer".
    Noura A A Ebrahim, Thoraya A Farghaly, Soliman M A Soliman.
      Exosomes are increasingly recognized as central regulators of organ-specific metastasis, and this review concentrates on their contribution to lung-directed dissemination. Yet, a detailed and integrative synthesis of how exosomes contribute to lung-directed metastatic spread-and what these mechanisms mean for clinical translation-remains largely absent from the current literature. Extracellular vesicles (EVs), particularly exosomes measuring 30-150 nm, are nanoscale, lipid bilayer-enclosed structures secreted by nearly all cell types. In cancer, tumor-derived exosomes act as potent mediators of intercellular signaling, enabling metastatic spread by modulating inflammation, angiogenesis, extracellular matrix dynamics, and immune evasion. Their molecular cargo, especially integrin profiles, plays a decisive role in determining metastatic tropism: integrins α6β4 and α6β1 are strongly associated with pulmonary colonization, while αvβ5 directs metastasis toward the liver. In malignancies such as breast, colorectal, melanoma, and pancreatic cancer, exosomal proteins and RNAs remodel the lung microenvironment, enhancing vascular permeability and attracting stromal and immune components that establish a receptive pre-metastatic niche. Clinically, exosomes are emerging as powerful liquid biopsy biomarkers and as promising platforms for targeted drug delivery. Advances in EV bioengineering now permit tailoring of surface molecules and cargo to improve pulmonary selectivity, for instance, supporting selective delivery of therapeutic payloads to pulmonary tumors or altering immune dynamics within the lung microenvironment, while omics-based and imaging technologies support detailed profiling and tracking. Early clinical trials of exosome-derived vaccines and therapeutic carriers have demonstrated feasibility and safety, although no EV-based therapy has yet achieved regulatory approval. This review integrates mechanistic insights, niche biology, and translational advances to highlight the unique role of exosomes in lung-specific metastasis and their potential as diagnostic and therapeutic tools in precision oncology.
    Keywords:  Cancer biomarkers; EV engineering; Exosomes; Extracellular vesicles; Integrins; Liquid biopsy; Lung tropism; Metastasis; Organotropism; Pre-metastatic niche; Targeted drug delivery
    DOI:  https://doi.org/10.1007/s12032-025-03217-y
  3. Med Oncol. 2025 Dec 26. 43(2): 78
    The role of exosomal long non-coding RNAs in head, neck and thyroid cancers.
    Esra Guzel Tanoglu, Zeynep Kilinc, Seyfure Adiguzel, Fatma Rumeysa Uzun, Irem Nur Ayla.
      Exosomal long non-coding RNAs (lncRNAs) have emerged as critical regulators in the pathogenesis, progression, and metastasis of head, neck, and thyroid cancers. These molecules, encapsulated within exosomes and released into biological fluids, mediate intercellular communication and influence various oncogenic processes including epithelial-mesenchymal transition (EMT), angiogenesis, immune evasion, and therapy resistance. Recent studies have demonstrated that specific exosomal lncRNAs are differentially expressed in cancer patients compared to healthy individuals, making them promising candidates for non-invasive biomarkers in early diagnosis, prognosis assessment, and treatment monitoring. In addition, several exosomal lncRNAs actively participate in modulating the tumor microenvironment, supporting cancer cell proliferation, migration, and metastatic potential. Therapeutically, targeting oncogenic lncRNAs or restoring tumor-suppressive ones offers new strategies for overcoming drug resistance and enhancing treatment efficacy. However, there are some areas of ambiguity and conflicting data in this topic. Thus, despite their promise, further large-scale and longitudinal studies are needed to validate their clinical utility of exosomal lncRNAs. This review summarizes the current knowledge on the biological functions and clinical applications of exosomal lncRNAs in head, neck, and thyroid cancers, highlighting their potential as biomarkers and therapeutic targets in modern oncology.
    Keywords:  Biomarker; Cancer; Exosome; Head and neck; Long non-coding RNA; Thyroid
    DOI:  https://doi.org/10.1007/s12032-025-03203-4
  4. Med Oncol. 2025 Dec 26. 43(2): 76
    Exosomal non-coding RNAs as emerging drivers of immune dysregulation in melanoma.
    Bahaa Ibrahim Saeed, Wesam R Kadhum, Muhammad Ikram Ullah, Jaafaru Sani Mohammed, Suhas Ballal, Abhayveer Singh, D Alex Anand, Samir Sahoo, Yasser Fakri Mustafa, Hanen Mahmod Hulail.
      Melanoma is a type of skin cancer that starts in melanocytes. It is estimated to increase by 2050 based on prediction studies. Exosomes have been identified as crucial intracellular mediators by carrying the donor-derived cargoes from stromal cells, immune cells, and even tumor cells, thereby affecting the function of recipient cells in a context-dependent manner. Although EVs can transport biologically active compounds like proteins, lipids, RNA, and DNA, their exact role remains unclear. The past few years have seen a surge in studies on tumor-associated cargo in exosomes, particularly concerning ncRNAs. The function of exosomal non-coding RNAs in melanoma's immunopathogenesis has been reviewed in detail in the current narrative review article. Exosomal ncRNAs have the potential to develop novel diagnostic and therapeutic targets in melanoma.
    Keywords:  Exo-ncRNA; Exosome; Immune system; Melanoma; ncRNA
    DOI:  https://doi.org/10.1007/s12032-025-03202-5
  5. Eur J Pharmacol. 2025 Dec 18. pii: S0014-2999(25)01255-5. [Epub ahead of print]1012 178501
    Therapeutic potential of microRNA let-7a-enriched exosomes in modulating macrophage plasticity (M1) and inhibiting malignant tendencies in breast cancer.
    Elmira Aghazadeh, Shahla Mohammad Ganji, Fatemeh Ashrafi, Ardeshir Abbasi.
      Tumor-associated macrophages (TAMs) play a pivotal role in cancer progression, and their polarization toward the M2 phenotype contributes to immune suppression and metastasis promotion. One promising immunotherapeutic approach involves reprogramming M2 macrophages into the pro-inflammatory and anti-tumor M1 phenotype within the tumor microenvironment. This study investigated the effect of exosomes derived from 4T1 breast cancer cells, loaded with microRNA let-7a, on macrophage polarization and tumor-related behaviors. Tumor-derived exosomes (TEXs) were isolated and characterized by DLS, Flowcytometry (CD63) and TEM, followed by let-7a loading via electroporation. Peritoneal macrophages from Balb/c mice were extracted, polarized into the immunosuppressive M2 phenotype, and subsequently treated with let-7a -enriched exosomes (TEX + let-7a), leading to their repolarization into M1 macrophages. Anti-cancer assays, including viability, apoptosis, metastasis, angiogenesis, and migration, were then performed. Results demonstrated that these engineered exosomes effectively repolarized M2 macrophages into active, tumor-suppressing M1 macrophages. The induced M1 macrophages significantly reduced cancer cell survival, increased apoptosis through elevated BAX/Bcl-2 ratio, and suppressed the expression of metastasis-associated (MMP2, MMP9) and angiogenesis-related (VEGF) genes. Moreover, cancer cell migration was markedly inhibited. Collectively, these findings indicate that let-7a -enriched exosomes can reprogram macrophage plasticity to effectively suppress malignant behaviors in breast cancer. This novel approach highlights the high therapeutic potential of targeted exosome-based miRNA delivery for refining tumor microenvironment regulation and advancing breast cancer immunotherapy strategies.
    Keywords:  Breast cancer; Cancer immunotherapy; Exosomes; Let-7a; Macrophage polarization
    DOI:  https://doi.org/10.1016/j.ejphar.2025.178501
  6. Reprod Biol Endocrinol. 2025 Dec 25.
    Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention.
    YanFeng Yang, BingJie Rui, Ji Hyang Kim.
      Exosomes are nanoscale vesicles that traffic bioactive cargo and modulate cell-cell communication within the ovarian niche. They are pivotal mediators in ovarian microenvironment-related premature ovarian insufficiency (omePOI): pathogenic exosomes propagate injury, whereas therapeutic Exosomes restore homeostasis to shape the niche and influence disease onset and course. However, omePOI still lacks sensitive predictive biomarkers and disease-modifying therapies; moreover, the complexity of the ovarian niche-encompassing extracellular matrix, stromal and immune compartments, vasculature, and metabolic-redox balance-poses substantial translational challenges. In this Review, we first summarize the current clinical challenges in diagnosing and managing omePOI. We then focus on reported correlations between exosomal alterations and omePOI, and postulate mechanisms by which these vesicles influence disease biology across apoptosis/mitochondrial injury, senescence, inflammation and innate-adaptive crosstalk, angiogenesis, fibrosis/extracellular matrix, and metabolic-redox pathways. Finally, we highlight the potential value of exosomal changes as biomarkers for predicting omePOI and discuss exosomal interventions, including mesenchymal stromal cell-derived and engineered Exosomes, as well as exosome-biomaterial composites together with design principles from ovarian tissue engineering.
    Keywords:  Biomarkers; Exosomes; Hydrogels; Ovarian microenvironment; Premature ovarian insufficiency
    DOI:  https://doi.org/10.1186/s12958-025-01514-9
  7. J Drug Target. 2025 Dec 24. 1-20
    Recent Advances in Theranostic-based Extracellular Vesicles in Cancer Stem Cell Diagnosis and Therapy.
    Yunlan Huang, Linlin Chang, He Wang, Huiyang Sun, Yibin Feng, Dongqing Li.
      Cancer remains a leading cause of mortality worldwide, with treatment failure and disease recurrence often driven by cancer stem cells (CSCs), which constitute a resilient subpopulation within tumors characterized by self-renewal, differentiation capacity, and resistance to conventional therapies. Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted by CSCs and play pivotal roles in tumor progression, immune evasion, and therapeutic resistance by transporting bioactive molecules such as heat shock proteins and regulatory RNAs. These vesicles reflect the molecular signature of their parent cells and offer unique opportunities for noninvasive diagnostics and targeted therapy. The theranostic paradigm, which integrates diagnostic and therapeutic functions, leverages EVs for CSC-specific biomarker detection, drug delivery, and real-time monitoring of treatment response. Advances in nanotechnology and molecular engineering have enabled the functionalization of EVs with imaging agents and therapeutic payloads, increasing their specificity and efficacy in preclinical and early clinical settings. This narrative review synthesizes current knowledge on CSC biology, EV biogenesis, and the evolving landscape of EV-based theranostics, highlighting translational progress, technical challenges, and future directions. Theranostic EVs represent a promising frontier in precision oncology, offering transformative potential for the management of CSC-driven tumorigenesis and relapse.
    Keywords:  Cancer Stem Cells; Extracellular Vesicles; Precision Oncology; Theranostics; Tumor Microenvironment
    DOI:  https://doi.org/10.1080/1061186X.2025.2609201
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